Neuroprotective effect of Salvia officinalis bioactive fraction against ischemic stroke in rats: LC-MS, in silico and in vivo insights

Oxidative stress and neuroinflammation are major contributors to cognitive and motor impairments after ischemic stroke. In this study, the protective effect of the bioactive fraction of Salvia officinalis was assessed in a bilateral carotid artery occlusion (BCCAO)-induced model of ischemic stroke in rats. The methanol extract was fractionated and screened for antioxidant and anti-inflammatory activity, with the n-hexane fraction being the most active. Rats were pretreated (14 days) with the n-hexane fraction (250 and 500 mg/kg, p.o.) and then underwent BCCAO. Behavioral tests revealed significant cognitive and motor impairment, as indicated by higher transfer latency in the plus maze and lower spontaneous alternation in the Y-maze (p < 0.001). Motor deficits were apparent through a higher beam walking time (p < 0.001) and lower fall-off time in the hanging wire test (p < 0.001). Biochemical analysis indicated lower levels of antioxidant enzymes (superoxide dismutase, catalase, glutathione, p < 0.001) and elevated malondialdehyde and myeloperoxidase (MPO) levels (p < 0.001). Neuronal damage was validated by triphenyl tetrazolium chloride staining, and histopathology established degeneration in the hippocampal dentate gyrus. LC-MS revealed luteolin, myricetin, protocatechuic acid, and limocitrin, which showed good Keap1–Nrf2 (−5.83, −4.90) and MPO (−7.02, −6.42) binding in docking experiments. The alleviation of oxidative stress, inflammation, and neuronal injury by the n-hexane fraction of S. officinalis affirms its neuroprotective capacity in post-stroke recovery.